Women experience adverse drug reactions, ADRs, nearly twice as often as men, yet the role of sex as a biological factor in the generation of ADRs is poorly understood. Most drugs currently in use were approved based on clinical trials conducted on men, so women may be overmedicated. We determined whether sex differences in drug pharmacokinetics, PKs, predict sex differences in ADRs. Searches of the ISI Web of Science and PubMed databases were conducted with combinations of the terms: drugs, sex or gender, pharmacokinetics, pharmacodynamics, drug safety, drug dose, and adverse drug reaction, which yielded over 5000 articles with considerable overlap. We obtained information from each relevant article on significant sex differences in PK measures, predominantly area under the curve, peak/maximum concentrations, and clearance/elimination rates. ADRs were identified from every relevant article and recorded categorically as female-biased, male-biased, or not sex-biased. For most of the FDA-approved drugs examined, elevated blood concentrations and longer elimination times were manifested by women, and these PKs were strongly linked to sex differences in ADRs. Of the 86 drugs evaluated, 76 had higher PK values in women; for 59 drugs with clinically identifiable ADRs, sex-biased PKs predicted the direction of sex-biased ADRs in 88% of cases. Ninety-six percent of drugs with female-biased PK values were associated with a higher incidence of ADRs in women than men, but only 29% of male-biased PKs predicted male-biased ADRs. Accessible PK information is available for only a small fraction of all drugs Sex differences in pharmacokinetics strongly predict sex-specific ADRs for women but not men. This sex difference was not explained by sex differences in body weight. The absence of sex-stratified PK information in public records for hundreds of drugs raises the concern that sex differences in PK values are widespread and of clinical significance. The common practice of prescribing equal drug doses to women and men neglects sex differences in pharmacokinetics and dimorphisms in body weight, risks overmedication of women, and contributes to female-biased adverse drug reactions. We recommend evidence-based dose reductions for women to counteract this sex bias.

中文翻译：

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药代动力学中的性别差异可预测女性药物不良反应。

女性经历不良药物反应，ADR的频率几乎是男性的两倍，但人们对性别作为ADR产生的生物学因素的作用知之甚少。目前使用的大多数药物都是根据对男性进行的临床试验批准的，因此女性可能用药过度。我们确定药物药代动力学，PK中的性别差异是否可预测ADR中的性别差异。使用以下术语的组合对ISI Web of Science和PubMed数据库进行了搜索：药物，性别，药代动力学，药效学，药物安全性，药物剂量和药物不良反应，共产生了5000篇文章，有相当多的重叠之处。我们从每篇相关文章中获得了有关PK度量的显着性别差异，曲线下主要面积，峰值/最大浓度和清除/清除率的信息。在每篇相关文章中都确定了ADR，并将其分类为女性偏爱，男性偏爱或未性别偏爱。对于大多数经FDA批准的药物，女性表现出较高的血药浓度和更长的消除时间，并且这些PK与ADR的性别差异密切相关。在评估的86种药物中，有76种具有较高的PK值。对于59种临床上可识别的ADR药物，性别偏向的PK预测了88％的病例中性别偏向的ADR的方向。在女性偏爱的PK值中，有96％的药物与女性相比，男性的ADR发生率更高，但是男性偏爱的PK预测只有29％的男性偏爱ADR。可访问的PK信息仅可用于所有药物的一小部分。药代动力学中的性别差异强烈预测女性而非男性的性别特异性ADR。性别的差异不能用体重的性别差异来解释。在公开记录中缺乏针对数百种药物的按性别分层的PK信息，这引起了人们的担忧，即PK值中的性别差异普遍存在并且具有临床意义。对男性和女性开处方均等剂量的普遍做法忽略了药代动力学的性别差异和体重的二态性，存在女性过度用药的风险，并导致女性偏向药物不良反应。我们建议减少妇女的循证剂量，以抵消这种性别偏见。对男性和女性开处方均等剂量的普遍做法忽略了药代动力学的性别差异和体重的二态性，存在女性过度用药的风险，并导致女性偏向药物不良反应。我们建议减少妇女的循证剂量，以抵消这种性别偏见。对男性和女性开处方均等剂量的普遍做法忽略了药代动力学的性别差异和体重的二态性，存在女性过度用药的风险，并导致女性偏向药物不良反应。我们建议减少妇女的循证剂量，以抵消这种性别偏见。